Is there anything you are so passionate about that you would continue to pursue for decades even if you didn’t see success? This episode features a story of unwavering dedication and persistence.
I also include some recent FAQs about my job as a pharmacist in a pediatric hospital.
Have you ever had an idea that you felt very invested in but never quite caught on? Maybe it was something you pitched to someone else and got rejected a couple of times? How long would you keep going before scrapping the idea? Probably a couple of rejections and I’d be ready to move on.
This episode is about one of the greatest, world-changing stories of persistence I’ve ever heard. I recently heard about it from her own words in another Podcast that I will link in the show notes.
Persistent: continue firmly or obstinately in an opinion or a course of action in spite of difficulty, opposition, or failure.
Remember that as we progress through this story and think about what it is in your life that you are that passionate about or determined to follow through that you would continue to pursue no matter what obstacles arise in your path.
This story is about a girl named Kati that grew up in a small town in Hungary. Born in 1955, she came from very humble beginnings, without many of the conveniences we enjoy today. Her father was a butcher and she credits this to her early interest in biology by seeing him slaughtering animals. She took that love of biology and decided to pursue science at a university in Hungary where she ultimately earned her Ph.D. After the lab where she was working in Hungary shut down and her position was eliminated, she and her husband and 2-year old daughter immigrated to the U.S. They could only withdraw a small amount of money from their bank before leaving the country so they took what little they had and hid it in their daughter’s teddy bear so that they would not be completely destitute once they arrived in the U.S.
After moving to the United States, Kati completed her post-doctoral work at Temple University in Pennsylvania for a few years in the late 80s. She then went on to become an assistant research professor at the University of Pennsylvania in 1990. In order to obtain funding for her research, Kati had to write grants. Because her work was in a newly emerging field of RNA research, she had difficulty obtaining funding. Her grants were rejected over and over and over. The technology just wasn’t there to be able to synthesize the molecules she wanted to study inside of a lab. It was too high risk and no one wanted to fund it.
Kati’s work progressed to focusing on messenger ribonucleic acid or mRNA. I think you know where I’m going with this. If those four letters make you uncomfortable, I invite you to stay. To think about it differently for the first time or even in a new way. To humanize the story and appreciate the determination and persistence of Dr. Kati Kariko.
So let’s review a basic definition of what this means in terms of genetics:
mRNA molecules carry the genetic information needed to make proteins. They carry the information from the DNA in the nucleus of the cell to the cytoplasm where the proteins are made.
I am not a geneticist so I need to break it down to the simplest terms: mRNA carries a protein blueprint from a cell’s DNA to its ribosomes, which are the machines that drive protein synthesis.
Let’s go back to Kati’s research focus. It was only just a few years earlier in the late 80s that scientists had even figured out how to synthesize mRNA, to create it from scratch in a lab. She initially wanted to work on mRNA therapies that could help improve blood vessel transplants by producing proteins that could keep newly transplanted vessels alive.
The biggest problem at the time was that when the synthesized mRNA therapy was injected into lab animals, they had such a severe inflammatory response that they died. She had to figure out how to get the immune system to not recognize the mRNA as foreign to have such a severe inflammatory reaction.
By 1995, she was demoted back to a low-level academic research position because the mRNA research seemed to have hit a dead end. At the same time, her husband was stuck in Hungary for 6 months due to a green card issue and she was also diagnosed with cancer. At that point, I definitely would have given up. Ten years without much, if any, success, her family life was a mess, and she’d just received a life-altering diagnosis: enough. But, nevertheless, she persisted.
Some time went by and Kati had a chance encounter at a copy machine with an immunologist at the University of Pennsylvania, Dr. Drew Weissman. Kati was able to form a partnership with Dr. Weissman, who had the funding and status to help her, and together they were able to determine that one of the four nucleosides that formed the mRNA, uridine, was causing the inflammatory reactions of the immune systems. They were able to replace uridine with an analog that looked the same but did not cause the reactions. When the lab mice were injected with the modified mRNA, they didn’t have that inflammatory reaction and they lived. They published their data and no one really seemed to notice.
A couple of scientists did notice, which led to two biotech companies ultimately using this technology to focus on vaccine development. The two companies were BioNTech (which later partnered with Pfizer) and Moderna. Their research had previously focused on a potential Zika vaccine and influenza vaccines. After the start of the Covid-19 pandemic, once the DNA of the coronavirus was sequenced, the two companies were able to focus in on designing their mRNA vaccine. The vaccines work by a different mechanism than what has previously been the traditional route of taking a tiny piece of inactivated (or live) virus and introducing it to the immune system to facilitate an immune response. Instead, the mRNA is introduced into the body to briefly instruct cells to produce the coronavirus’s spike protein. If the coronavirus then entered the body later, the spike protein on the virus would be recognized as an invader and attacked by the immune system.
And that is the story of how COVID vaccines were tested, analyzed, produced, and made so readily available in record time. After decades of research, the technology was already in place to make it happen. There are so many interesting perspectives on Dr. Kariko’s contribution to the COVID vaccines and her own thoughts from interviews that I find fascinating. This is a very abbreviated version so I will have some of my favorite articles linked in the show notes.
I wholeheartedly admire Dr. Kariko and her unending persistence. When everything was crumbling around her, and no one cared about what she was doing, many people would have taken that as a sign that it was time to move on. But she never wavered. She always felt that there was more to be uncovered—more questions to be answered and more opportunity to perfect her ideas.
Some may not always see science as creative but I think this story highlights how much creativity there really is in science. It was certainly a very methodical process but Dr. Kariko literally created mRNA through synthesis and then utilized that mRNA to work on solving nearly limitless conditions. As someone that subscribes to the idea of creationism, I personally see science as the explanation of what was created through divine design and utilizing those same mechanisms for the betterment of society. I don’t believe that they are opposing forces or that one has to have concrete delineations between the two.
In my work as a pharmacist, I do get asked from time to time about what I am seeing at work in a pediatric hospital and about the vaccination.
So as of the airing of this episode, there has been a lot of discussion as of late about the impact COVID has on children. Whether there is a need for masks, or vaccinations, or whether school should be in-person or virtual. These are all very personal decisions we need to make and can sometimes be difficult to put a blanket statement on. I know that this is a very polarizing topic. Mask mandates have been a specific hot button issue with the argument that a small number of children have died. And that is true in comparison to adults. I follow news headlines and articles around this topic fairly closely. You may have seen that pediatric hospital admissions for COVID are on the rise. We are definitely seeing that in our area. I’m just not seeing a lot of conversation about what actually happens to children that are hospitalized.
We can group the types of admissions for children with COVID we get into two categories: acute COVID and multisystem inflammatory syndrome in children, or MIS-C. The first being acute COVID. These symptoms are most similar to a typical adult presentation: respiratory symptoms ranging from mild and progressing to pneumonia to respiratory distress or sepsis or septic shock. We’ve had neonates to teenagers with these symptoms. I get asked a lot about comorbidities or underlying conditions and there have been some with obesity or diabetes, even some that are diagnosed at the same time with type-1 or type-2 diabetes while they have acute COVID, or cerebral palsy or cardiac issues, but I would say that we still have a majority of pediatric patients with no significant past medical history. Depending on their disease severity, these kids can receive supportive care like fluids for dehydration, steroids, and the antiviral drug remdesivir that has been used in adults. There is a monoclonal antibody that has been used in some pediatric patients that are hospitalized called tocilizumab or Actemra but I’m not aware of any patients that have been on it at my particular hospital as of yet and most of the data recommending its use is from adults. There is a higher risk of blood clots with acute COVID so depending on their risk category, kids may receive aspirin or a different type of blood thinner shot. We’ve had a handful of kids that have had to be intubated as well. So far, most have recovered within a few days to a week and are able to go home.
For the other category, MIS-C, this commonly occurs within a few weeks after having or being exposed to COVID. So right now while we are at another peak of admissions for acute COVID, there is a high probability that in a few weeks we will have more MIS-C cases. The case definition for MIS-C is age 21 years or younger, fever for at least 24 hours, specific laboratory markers of inflammation, severe illness requiring hospitalization, with multisystem organ involvement including at least 2 of the following: cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological. So some common presenting symptoms are fever, GI upset like vomiting and diarrhea, head to toe rash, low blood pressure or feeling like they’re going to faint, and being much more tired and sleepy than normal. Treatments for MIS-C are different than acute COVID. Most get a cardiology consult and an echocardiogram of their heart to look at its function. If their blood pressure is really low, they’ll be given medication to help support a higher blood pressure or help their heart pump more efficiently. They’ll also be given IV immune globulin (or IVIG) infusions to help give extra antibodies to fight infection as well as steroids. There is still a higher risk of blood clots like with acute COVID, so depending on the risk category, they’re given aspirin or blood thinner shots. Again, as far as underlying conditions, we’ve had mostly kids without any significant past medical history that have been treated for MIS-C at the hospital where I work. The youngest one I remember so far has been preschool age and all the way up through teenagers.
These examples of treatments are very fluid. They could change from time to time depending on new studies and fluctuations in variants and so many other variable factors.
Statistically children have had a much better go at COVID than adults but they are not immune to it or exempt from illness due to age. Because of the higher number of overall cases currently happening in the US, there are bound to be more in children and thus more hospitalizations.
So when the topic of masks in schools comes up, especially, and most importantly, for children that are too young for vaccine eligibility, it’s really upsetting to see such dramatic outbursts from parents screaming at school board members and healthcare professionals that advocate for masks in schools. I think that as a society our opinions are often formed from our experiences and perspectives. If someone hasn’t seen a child (or dozens of children) very ill with COVID, it would be easy to say that it’s no big deal, that there’s no reason kids need to wear masks. I wonder if maybe their opinions might be different if they had. Because of my perspective and my experience, I disagree. Not only are there children that are immunocompromised for various reasons that would not fare well from a serious infection, there is the potential for even a typical “healthy” kid to become very ill from the virus. This isn’t fear mongering either. Again, it is a low percentage.
The other issue is that with the high transmissibility of the delta variant that is currently the most prevalent form of the virus circulating in the U.S., there is a high likelihood that a lot of kids could become sick at the same time if no precautions are taken in school settings. I’m not very adept in epidemiology but I recently read an article that I thought was really interesting about how epidemiologists track how easily diseases spread through a metric called the basic reproductive number or “R naught.” Ro is the average number of susceptible people that each infected person is expected to infect. If Ro is larger than one, infections will continue to grow exponentially until herd immunity is reached in one way or another. If Ro is less than one, it will eventually dissipate. So in this article some examples of Ro were with the 1918 influenza pandemic, the average infected person could have passed on the disease to between two and three people, giving it an Ro of between 2 and 3. The original COVID-19 virus in Wuhan, China had an Ro between 2.3 and 2.7; the alpha variant had an Ro between 4 and 5; and the delta variant is on par with chicken pox which has an Ro between 9 and 10. With this trend, what will future variants look like? Keeping this in mind, children that are infected in school or infect others in school do not leave it there. Infection then goes on to spread to others they’re around and throughout the community.
At the beginning of the summer, when vaccinations of the general adult population were at their highest, our overall COVID hospital admissions in adults were so low and non-existent in pediatrics for a month or two. But then vaccinations stalled and the prevalence of the delta variant increased, and we had spike in pediatric cases over the summer. I’m several layers removed from the front lines and I’m so burned out. I felt really hopeful when our numbers were so low that we were going to wrap this up. I can’t imagine how healthcare workers feel that deal directly with these sick patients day in and day out.
There is always something heavy going on in the world. From this pandemic, to natural disasters, to terrorism, to racism and sexism, injustices everywhere, it’s a lot. And it’s natural to want to do something to help. With this one though, there are a couple of easy things that can be done. This isn’t new information. We’ve all heard it. Wear a mask and get vaccinated. I know that there is no amount of discussion that would ever convince some groups to be vaccinated. I’m not going down that road. I’m too tired to do that anymore. But if someone has been thinking that they want to wait it out and see how others do with this new kind of vaccine, I can identify with that. I had several coworkers that participated in the vaccine trials in Las Vegas and I was always too scared to be in a trial myself. When there was discussion of vaccines being offered to healthcare workers, I had decided initially that I was far enough removed that I wasn’t in a high risk category for exposure and that I would wait it out and see how it went for others first before I got mine. As the opportunity got closer and closer, I read more about how the vaccine worked and results of the trials and I decided that “enough” people had already received the vaccine with such positive outcomes that I felt good about it. If you find yourself still in that category, have you thought about what your “enough” looks like?
I’ve also been asked by friends and family members if I will have my children receive the COVID vaccine when it becomes available. The answer is unequivocally “yes.” I wish they could have already been vaccinated prior to school starting but as soon as they’re eligible, they’ll get it. I’ve been asked about the concern around infertility. That was an early claim from misinformation and has been repeatedly debunked, along with microchips and causing magnetization. The CDC has recommended vaccination during pregnancy as well. We’ve had several premature births at my hospital from complications of COVID in pregnant mothers.
If you’re still in the hesitant or undecided camp, stop reading opinions on social media. Don’t believe everything you read on the internet, especially social media. In college and in residency I was taught to read medical studies for myself, not to just rely on the authors’ conclusion. The same applies to what’s on the internet. Don’t get tangled in rhetoric. Research for yourself. Go straight to the source. Talk to your healthcare provider. Talk to a healthcare professional you know and trust. If you think it may be too late to get vaccinated or what’s the use with new variants popping up all over the place? It’s not too late. They’re still very effective against severe disease even in spite of variants. If it takes incentives like lotteries or admittance for indoor dining or being able to attend concerts or sporting events, or worst case scenario losing a loved one, so be it. Vaccine cards don’t include a reason, however altruistic or otherwise.
If you’ve made it all the way through, thanks for sticking around. I don’t plan on spending too much of this podcast on medical topics, especially one so polarizing as this one. I do this podcast as a creative outlet but I also think that Dr. Kati Kariko’s story is so inspiring. Through all of her setbacks, she persisted. She never gave up. She took a lot of risks and she has finally been able to see the benefits of her hard work and determination.
As always, I hope you can use these ideas as tipping off points to channel the ambition, curiosity, and desire to create the life you want to live. Thanks so much for listening. Our time is so important and I am so appreciative that you spent some of it with me.